The development of malignant lymphoma in both mice and man appears to reflect a neoplastic change occurring in the immune system. The SJL/J lymphoma, which occurs in greater than 80% of the mice after 10 months of age, appears to develop through a specific type of lymphoid hyperplasia very similar to that often seen in humans that eventuate in large cell ("histiocytic" or immunoblastic) lymphoma that is strikingly similar to the SJL/J lymphoma. We propose to examine SJL/J mice in the presumably preneoplastic stages of their disease to ascertain if malignant transformation can be demonstrated in vitro by mitogen stimulation with LPS. By studying the B-cell response to mitogen in the spontaneous as well as in the graft vs. host and drug-induced (dilatin) models of the lymphoma, we plan to study the role of proliferation and differentiation in the lymphomatous process. In addition, immuno-suppression (mu suppression) will be studied to ascertain its effects on lymphomagenesis, both in vivo and in vitro.